Ustekinumab improves health-related quality of life in patients with moderate-to-severe Crohn's disease: Results up to week 104 of the STARDUST trial

Panes J, Vermeire S, D’Haens GR, et al., STARDUST Study Group

United European Gastroenterol J 2023 May 4. doi: 10.1002/ueg2.12384. Online ahead of print.

Introduction

The concept of treat to target (T2T) in Crohn’s Disease (CD) involves optimising therapy until a predetermined clinically relevant endpoint is met. In recent years, this endpoint has most commonly been a short-term biomarker response or endoscopic healing, but this has typically been juxtaposed with long-term patient reported outcomes (PROs) such as health-related quality of life (HRQoL) [1]. The international STRIDE-2 guidelines emphasise the need for monitoring at frequent intervals to ensure that treatment targets agreed at the commencement of any therapy are actually being achieved. One of the big unknowns of such strategies, requiring frequent monitoring, has been their cost-efficiency. However, concerns about cost have been balanced by arguments that adequate monitoring may allow earlier and more appropriate initiation of advanced therapies, which may then result in better longer-term outcomes [2].

STARDUST (NCT03107793) was a phase 3b, open-label, randomised controlled trial that compared ustekinumab (UST) T2T with standard-of-care (SoC) treatment strategies in adult patients with moderate to severe CD. The primary results from this trial have previously been reported, and it is notable that endoscopic and biomarker endpoints were not statistically different between the two treatment strategies [3]. However, it is also worth noting that while more patients in the T2T arm received q4w (4-weekly) dosing of UST (18.4% vs 0%), more patients in SoC received q8w (8-weekly) dosing (61.5% vs 38.8%). The original STARDUST trial included 440 patients, of whom 336 completed the first year of treatment and 323 (T2T, n=147; SoC, n=176) were subsequently enrolled to the long-term extension (LTE) period until week 104 (2-year mark). In this study, Panes et al. report on the HRQoL outcomes from patients in the LTE study from the STARDUST trial.

Efficacy of filgotinib in patients with ulcerative colitis by line of therapy in the phase 2b/3 SELECTION trial

Dotan I, Feagan BG, Taliadouros V, et al.

J Crohns Colitis 2023 Mar 16. doi:10.1093/ecco-jcc/jjad039. Online ahead of print.

Introduction

In recent years, there has been significant optimism in the field with the arrival of newer licensed therapies for patients living with IBD [1]. Alongside the welcome arrival of new therapeutics, there has also been an appreciation that many (but not all) patients may have preferences for oral medications [2]. In particular, targeting Janus kinases (JAKs) with oral small molecule treatments has proved to be a promising strategy. Indeed, tofacitinib, a pan-JAK inhibitor, was shown to have efficacy in patients with Ulcerative Colitis (UC), even in some instances where there had been loss of response or non-response to all prior licensed biologic options [3]. With growing understanding of the pathways involved in UC, preferential inhibition of JAK1 has been investigated in the field of IBD, including with the JAK1 inhibitor, filgotinib. This is a medication already licensed for some rheumatological conditions and it was recently assessed in the context of UC in the phase 2b/3 SELECTION trial – with the results having previously been published, and demonstrating superiority of filgotinib over placebo in UC [4]. In this current study, Dotan et al. assess efficacy of filgotinib based on prior treatment exposure and number of lines of therapy for instances of previous exposure to biologic therapy, based on a post-hoc analysis of data from the SELECTION trial. This study contributes to our understanding of how to sequence and position a new advanced therapy, in the context of a growing armamentarium of treatment options for patients living with UC.

Dear Y-ECCO Friends,

Although it still feels as though ECCO’23 has only just exited our rear-view mirrors, I’m sure many of you have moved onto preparing your abstract submissions and it’s worth remembering that the abstract submission window for ECCO’24 will soon be open! However, before getting started with that (there’s still plenty of time, after all) I would very much encourage you to take a look at the recently published IBD Communication Toolbox. Whatever type of ECCO Membership you hold, I can assure you that there’s something there for everyone.

Robin Dart © ECCO

The return of a physical ECCO Congress finally gave me the chance to interview people in person for ECCO News. So, after an early morning start, the outgoing Chair of Y-ECCO, Charlotte Hedin, and I sat down to talk about what led her into gastroenterology, the impact of moving country mid-career and the Y-ECCO Communication Toolbox, which has recently been made available on the ECCO e-Learning Platform.

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): A randomised, double-blind, controlled, phase 2, proof-of-concept trial

Feagan BG, Sands BE, Sandborn WJ, et al.

Lancet Gastroenterol Hepatol 2023;8:307–20.

Introduction

Despite a growing armamentarium of advanced therapies for Ulcerative Colitis (UC), fewer than 40% of patients maintain clinical remission at 12 months [1]. Combination therapy utilising dual biologic or small molecule agents can be considered in highly selected, medically refractory cases; however, robust data to support dual therapy in routine clinical practice are still lacking [2]. Inhibitors of TNF-α and IL-23 have demonstrated efficacy in the treatment of UC [3,4]. Data emerging from animal studies have suggested that their use in combination reduces colitis synergistically and may be more efficacious than treatment with either monotherapy [5].

This randomised double-blinded controlled phase 2 trial, named the VEGA trial, was conducted across 54 sites internationally and aimed to determine the efficacy and safety of combination therapy with guselkumab (GUS), an IL-23 p19 antagonist, plus golimumab (GOL), a TNF-α inhibitor, compared with either monotherapy in UC.

Point-of-care intestinal ultrasound in IBD patients: Disease management and diagnostic yield in a real-world cohort and proposal of a point-of-care algorithm

Bots S, De Voogd F, De Jong M, et al.

J Crohns Colitis 2022;16:606–615.

Introduction

Intestinal ultrasound (IUS) is an inexpensive, non-invasive, safe and repeatable, dynamic cross-sectional imaging technique for IBD. It has been demonstrated to be accurate and reliable both for initial diagnosis of IBD and for follow-up monitoring [1]. Huge advantages of IUS are that it does not need any prior preparation of the patient and provides a real-time result. IUS can be performed in various hospital settings, which makes it the only point-of-care (POC) imaging technique available today [2].

The impact of POC IUS on daily decision making and the evolution in its use over the years were evaluated in this retrospective study, which included two consecutive cohorts of IBD patients in a real-world outpatient setting. The first cohort of patients, included between January 2016 and July 2018, was compared with a second cohort collected between October 2019 and December 2019.

Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn’s disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial

Louis E, Resche-Rigon M, Laharie D, et al; GETAID and the SPARE-Biocycle research group

Lancet Gastroenterol Hepatol 2023;8:215–27.

Introduction

Therapeutic strategies for Crohn’s Disease have evolved over the past decade, with mounting evidence that achieving deep remission (defined as clinical, biochemical and endoscopic remission) is associated with better long-term outcomes [1, 2]. Combination therapy with infliximab and azathioprine has been shown to be superior to either infliximab or azathioprine monotherapy in achieving clinical remission and endoscopic healing in azathioprine-naive patients, thus supporting the paradigm of early disease management and the use of treatment combinations to increase treatment success [3]. Concerns regarding the implications of long-term combination therapy, such as infections and lymphoproliferative disorders, have provided the rationale for a formal clinical trial of treatment de-escalation.

The aim of this trial was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy.

After two consecutive virtual events, the Y-ECCO Basic Science Workshop was back with a face-to-face meeting, reaching its 9^th edition on March 1, 2023, in Copenhagen.

This Workshop aims to involve young fellows in a fully comprehensive manner, giving them the opportunity to present relevant data that were submitted for the scientific programme and discuss their views with successful key opinion leaders in the field of Inflammatory Bowel Diseases (IBD), with special focus on basic and translational research. All sessions open with a hot topic presented by an invited senior specialist, followed by excellent presentations by selected young researchers. The secret of the constant success of this initiative is the friendly atmosphere, which allows participating Y-ECCO Members to increase their knowledge while also preparing for more challenging stages.

Dear Y-ECCO Friends,

I do hope you all enjoyed the ECCO Congress in Copenhagen and made the most of the opportunity to “get physical” again for the first time in too long! I’m sure many will agree that, although virtual conferencing has its positives, much of what makes ECCO such a special organisation to be part of can only be fully realised in person. The fact that this year’s meeting was the first in-person ECCO Congress since before the pandemic only added to the sense of excitement, and the meeting’s content did not disappoint. As is often the case, contributions from Y-ECCO Members made up a sizeable proportion of the original research presented: 58 oral presentations were selected to be presented by Y-ECCO Members and a total of ten Y-ECCO Members were awarded prizes. This again underscores the essential role played by Y-ECCO within ECCO, as a new generation of IBD experts are ushered in. 

Robin Dart © ECCO

Krisztina Gecse is a consultant gastroenterologist at the Amsterdam University Medical Centre. She is well known to ECCO as a past Chair of ClinCom and is now at the forefront of the international push towards bowel ultrasound as President Elect of the International Bowel Ultrasound Group. I met with her to hear about her journey from Hungary to Amsterdam and how bowel ultrasound might just be your future….